Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 81
Filter
1.
Article in English | MEDLINE | ID: mdl-38944417

ABSTRACT

While there is a large body of evidence indicating that sexual minority youth experience inequitably high rates of mental health problems (eg, depression, suicidality), we know little about how temporal changes in sexual attractions, identities and behaviour may impact mental health (and other) outcomes. In this essay, we review existing research regarding sexual fluidity and mental health among young adults in order to identify critical knowledge gaps with respect to an epidemiological understanding of the relationship between these factors. We describe three gaps that in turn inform a larger public health research agenda on this topic. First, there are a number of methodological challenges given that fluidity can occur over short or long periods of time and across multiple dimensions of sexual orientation (eg, attractions, identities and behaviour) with various patterns (eg, directionality of change). Tailored measures that accurately and inclusively reflect diversities of sexual fluidity trajectories are needed. Second, causal relationships between sexual fluidity and mental health remain uncertain and unquantified. Third, little is known about how features of context (eg, gender norms and political climate) influence youth experiences with sexual fluidity and mental health. Finally, we propose a set of recommendations to address these knowledge gaps to improve the quality of epidemiological research involving young people.

2.
Soc Sci Med ; 353: 117057, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38905923

ABSTRACT

Children with experience of maltreatment, abuse or neglect have higher prevalence of poor mental health. In the United Kingdom, child protection services identify children at risk of significant harm on the Child Protection Register (CPR) and intervene to reduce risk. Prevalence and incidence of mental health service use among this population of children are not well understood. We analysed records from one Scottish Local Authority's CPR, linked to electronic health records for all children in the broader health board region aged 0-17 years. We described mental health service use among children with a CPR registration using measures of mental health prescribing and referrals to child and adolescent mental health services (CAMHS). We calculated age- and sex-specific incidence rates for comparison with the general population. Between 2012 and 2022, we found 1498 children with a CPR registration, with 69% successfully linked to their health records. 20% were registered before birth and median age at registration was 3 years. Incidence rates in all measures of mental health service use were higher in children with a CPR record across all ages (at outcome) and genders compared to the general population. The largest absolute difference was for boys aged 5-9 with a CPR record, who had 31.8 additional mental health prescriptions per 1000 person-years compared to the general population (50.4 vs. 18.6 prescriptions per 1000 person-years, IRR: 2.7). Girls aged 0-4 years with a CPR registration had the largest relative difference, with a rate of CAMHS referral 5.4 times higher than the general population (12.3 vs. 2.3 per 1000 person-years). Our reproducible record linkage of the CPR to health records reveals an increased risk of mental health service use during childhood. Our findings have relevance to public mental health surveillance, service prioritisation and wider policy aiming to reduce childhood exposure to risk of harm.


Subject(s)
Child Abuse , Child Protective Services , Mental Health Services , Humans , Child , Male , Female , Adolescent , Child, Preschool , Mental Health Services/statistics & numerical data , Infant , Scotland/epidemiology , Child Protective Services/statistics & numerical data , Child Abuse/statistics & numerical data , Registries , Infant, Newborn , Incidence , Electronic Health Records/statistics & numerical data , Medical Record Linkage/methods
3.
Nephrol Dial Transplant ; 39(3): 426-435, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-37573145

ABSTRACT

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.


Subject(s)
Acute Kidney Injury , Kidney , Male , Female , Humans , Aged , Creatinine , Cohort Studies , Acute Disease , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Retrospective Studies
4.
BMC Psychiatry ; 23(1): 22, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36627578

ABSTRACT

BACKGROUND: One in eight children in the United Kingdom are estimated to have a mental health condition, and many do not receive support or treatment. The COVID-19 pandemic has negatively impacted mental health and disrupted the delivery of care. Prevalence of poor mental health is not evenly distributed across age groups, by sex or socioeconomic groups. Equity in access to mental health care is a policy priority but detailed socio-demographic trends are relatively under-researched. METHODS: We analysed records for all mental health prescriptions and referrals to specialist mental health outpatient care between the years of 2015 and 2021 for children aged 2 to 17 years in a single NHS Scotland health board region. We analysed trends in prescribing, referrals, and acceptance to out-patient treatment over time, and measured differences in treatment and service use rates by age, sex, and area deprivation. RESULTS: We identified 18,732 children with 178,657 mental health prescriptions and 21,874 referrals to specialist outpatient care. Prescriptions increased by 59% over the study period. Boys received double the prescriptions of girls and the rate of prescribing in the most deprived areas was double that in the least deprived. Mean age at first mental health prescription was almost 1 year younger in the most deprived areas than in the least. Referrals increased 9% overall. Initially, boys and girls both had an annual referral rate of 2.7 per 1000, but this fell 6% for boys and rose 25% for girls. Referral rate for the youngest decreased 67% but increased 21% for the oldest. The proportion of rejected referrals increased steeply since 2020 from 17 to 30%. The proportion of accepted referrals that were for girls rose to 62% and the mean age increased 1.5 years. CONCLUSIONS: The large increase in mental health prescribing and changes in referrals to specialist outpatient care aligns with emerging evidence of increasing poor mental health, particularly since the start of the COVID-19 pandemic. The static size of the population accepted for specialist treatment amid greater demand, and the changing demographics of those accepted, indicate clinical prioritisation and unmet need. Persistent inequities in mental health prescribing and referrals require urgent action.


Subject(s)
COVID-19 , Secondary Care , Male , Female , Child , Humans , Infant , Routinely Collected Health Data , Mental Health , Pandemics , COVID-19/epidemiology , Referral and Consultation
5.
Ecol Modell ; 465: 1-109635, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34675451

ABSTRACT

The Chesapeake Bay is the largest, most productive, and most biologically diverse estuary in the continental United States providing crucial habitat and natural resources for culturally and economically important species. Pressures from human population growth and associated development and agricultural intensification have led to excessive nutrient and sediment inputs entering the Bay, negatively affecting the health of the Bay ecosystem and the economic services it provides. The Chesapeake Bay Program (CBP) is a unique program formally created in 1983 as a multi-stakeholder partnership to guide and foster restoration of the Chesapeake Bay and its watershed. Since its inception, the CBP Partnership has been developing, updating, and applying a complex linked modeling system of watershed, airshed, and estuary models as a planning tool to inform strategic management decisions and Bay restoration efforts. This paper provides a description of the 2017 CBP Modeling System and the higher trophic level models developed by the NOAA Chesapeake Bay Office, along with specific recommendations that emerged from a 2018 workshop designed to inform future model development. Recommendations highlight the need for simulation of watershed inputs, conditions, processes, and practices at higher resolution to provide improved information to guide local nutrient and sediment management plans. More explicit and extensive modeling of connectivity between watershed landforms and estuary sub-areas, estuarine hydrodynamics, watershed and estuarine water quality, the estuarine-watershed socioecological system, and living resources will be important to broaden and improve characterization of responses to targeted nutrient and sediment load reductions. Finally, the value and importance of maintaining effective collaborations among jurisdictional managers, scientists, modelers, support staff, and stakeholder communities is emphasized. An open collaborative and transparent process has been a key element of successes to date and is vitally important as the CBP Partnership moves forward with modeling system improvements that help stakeholders evolve new knowledge, improve management strategies, and better communicate outcomes.

6.
Ann Surg Oncol ; 28(12): 7809-7820, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34041626

ABSTRACT

BACKGROUND: Epithelial appendiceal neoplasms are uncommon peritoneal malignancies causing a spectrum of disease including pseudomyxoma peritonei (PMP). The optimal management is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete CRS (CCRS), recurrence develops in almost 45% of patients. No consensus exists for the optimal treatment of recurrent disease, with treatment strategies including repeat CRS, watch-and-wait, and palliative chemotherapy. This report aims to describe evolving management strategies for a large cohort with recurrence after CCRS. METHODS: This retrospective study analyzed a prospective database of patients with recurrence after CCRS for appendiceal neoplasms from 1994 to 2017 who had long-term follow-up evaluation with tumor markers and computed tomography (CT). RESULTS: Overall, 430 (37.6%) of 1145 PMP patients experienced recurrence at a median of 19 months. Of these 430 patients 145 (33.7%) underwent repeat CRS, 119 (27.7%) had a watch-and-wait approach, and 119 (27.7%) had palliative chemotherapy. The patients with recurrence had a median overall survival (OS) of 39 months, a 3-year survival of 74.6%, a 5-year survival of 57.4%, and a 10-year survival of 36.5%. In the multivariate analysis, the patients who had recurrence within 1 year after primary CRS (hazard ratio [HR], 3.55), symptoms at recurrence (HR, 3.08), a high grade of disease or adenocarcinoma pathology (HR, 2.94), signet ring cells (HR, 1.91), extraperitoneal metastatic disease (HR, 1.71), or male gender (HR, 1.61) had worse OS. The OS was longer for the patients who had repeat CRS (HR, 0.41). The patients who underwent repeat CCRS had a 3-year OS of 87.5%, a 5-year OS of 78.1%, and a 10-year OS of 67.9%. CONCLUSIONS: Dilemmas persist around the optimal management of patients with recurrence after CRS and HIPEC for appendiceal tumors. Selected patients benefit from repeat CRS, particularly those with favorable tumor biology and focal disease.


Subject(s)
Appendiceal Neoplasms , Hyperthermia, Induced , Pseudomyxoma Peritonei , Surgeons , Appendiceal Neoplasms/therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermic Intraperitoneal Chemotherapy , Male , Neoplasm Recurrence, Local/therapy , Pseudomyxoma Peritonei/drug therapy , Retrospective Studies , Survival Rate
7.
Environ Sci Technol ; 55(4): 2585-2596, 2021 02 16.
Article in English | MEDLINE | ID: mdl-33523627

ABSTRACT

Filter performance can be affected by bacterial colonization of the filtration media, yet little is known about how naturally occurring bacteria modify the surface properties of filtration media to affect colloidal removal. We used sand columns and simulated stormwater conditions to study the retention of model colloidal particles, carboxyl-modified-latex (CML) beads, in porous media colonized by naturally occurring bacterial strains. Colloid retention varied substantially across identical columns colonized by different, in some cases closely related, bacterial strains in a cell density independent manner. Atomic force microscopy was applied to quantify the interaction energy between CML beads and each bacterial strain's biofilm surface. We found interaction energy between CML and each strain was significantly different, with adhesive energies between the biofilm and CML, presumed to be associated with polymer-surface bonding, a better predictor of CML retention than other strain characteristics. Overall, the findings suggest that interactions with biopolymers in naturally occurring bacterial biofilms strongly influence colloid retention in porous media. This work highlights the need for more investigation into the role of biofilm microbial community composition on colloid removal in porous media to improve biofilter design and operation.


Subject(s)
Biofilms , Colloids , Filtration , Porosity , Surface Properties
8.
Proc Math Phys Eng Sci ; 476(2238): 20200077, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32831591

ABSTRACT

Recent reconstructions of total solar irradiance (TSI) postulate that quiet-Sun variations could give significant changes to the solar power input to Earth's climate (radiative climate forcings of 0.7-1.1 W m-2 over 1700-2019) arising from changes in quiet-Sun magnetic fields that have not, as yet, been observed. Reconstructions without such changes yield solar forcings that are smaller by a factor of more than 10. We study the quiet-Sun TSI since 1995 for three reasons: (i) this interval shows rapid decay in average solar activity following the grand solar maximum in 1985 (such that activity in 2019 was broadly equivalent to that in 1900); (ii) there is improved consensus between TSI observations; and (iii) it contains the first modelling of TSI that is independent of the observations. Our analysis shows that the most likely upward drift in quiet-Sun radiative forcing since 1700 is between +0.07 and -0.13 W m-2. Hence, we cannot yet discriminate between the quiet-Sun TSI being enhanced or reduced during the Maunder and Dalton sunspot minima, although there is a growing consensus from the combinations of models and observations that it was slightly enhanced. We present reconstructions that add quiet-Sun TSI and its uncertainty to models that reconstruct the effects of sunspots and faculae.

9.
Acta Crystallogr F Struct Biol Commun ; 75(Pt 11): 697-706, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31702583

ABSTRACT

A high-affinity anti-cocaine monoclonal antibody, designated h2E2, is entering phase 1 clinical trials for cocaine abuse therapy. To gain insight into the molecular details of its structure that are important for binding cocaine and cocaine metabolites, the Fab fragment was generated and crystallized with and without ligand. Structures of the unliganded Fab and the Fab fragment bound to benzoylecgonine were determined, and were compared with each other and with other crystallized anti-cocaine antibodies. The affinity of the h2E2 antibody for cocaine is 4 nM, while that of the cocaine metabolite benzoylecgonine is 20 nM. Both are higher than the reported affinity for cocaine of the two previously crystallized anti-cocaine antibodies. Consistent with cocaine fluorescent quenching binding studies for the h2E2 mAb, four aromatic residues in the CDR regions of the Fab (TyrL32, TyrL96, TrpL91 and TrpH33) were found to be involved in ligand binding. The aromatic side chains surround and trap the tropane moiety of the ligand in the complex structure, forming significant van der Waals interactions which may account for the higher affinity observed for the h2E2 antibody. A water molecule mediates hydrogen bonding between the antibody and the carbonyl group of the benzoyl ester. The affinity of binding to h2E2 of benzoylecgonine differs only by a factor of five compared with that of cocaine; therefore, it is suggested that h2E2 would bind cocaine in the same way as observed in the Fab-benzoylecgonine complex, with minor rearrangements of some hypervariable segments of the antibody.


Subject(s)
Antibodies/chemistry , Cocaine/immunology , Immunoglobulin Fab Fragments/chemistry , Amino Acid Sequence , Cocaine/analogs & derivatives , Cocaine/chemistry , Crystallization , Crystallography, X-Ray , Humans , Hydrogen Bonding , Ligands , Protein Domains , Recombinant Proteins/chemistry
10.
Breast Dis ; 38(3-4): 93-96, 2019.
Article in English | MEDLINE | ID: mdl-30909179

ABSTRACT

BACKGROUND: Axillary Ultrasound (AUS) is now performed as a protocol in every newly diagnosed breast cancer in most European countries. It is an inexpensive and sensitive tool in hands of a trained operator. All AUS negative patients undergo Sentinel Lymph Node Biopsy (SLNB), while AUS positive patients bypass SLNB and undergo axillary nodal clearance (ANC) as a standard protocol. We wish to analyse these two groups to see if ANC can be foregone in these patients. AIMS AND OBJECTIVES: To compare and analyse the axillary disease burden in early breast cancer patients, with positive axilla, detected by AUS+ Biopsy versus those patients with normal axillary ultrasound or negative axillary biopsy that underwent ANC due to positive SLNB. MATERIAL AND METHODS: A retrospective review of all patients who underwent axillary lymph node clearance following histologically confirmed positive ultrasound (US) axilla (year 2009-2014) was performed and was compared with data collected for patients with USG negative but SLNB (OSNA- One Step Nucleic Acid Amplification) positive axilla. RESULTS: Axillary clearances performed for positive US axilla yielded significantly more positive lymph nodes than SLNB/OSNA positive axilla (p = 0.00496). These patients also had larger primary tumours (median 33 mm versus 21 mm, p = 0.01242) of a higher grade. Almost half of the patients in AUS positive group (49%) had high axillary nodal burden (>4 LNs). This is in great contrast with AUS negative, SLNB/OSNA positive group where 82.7% of patients had <4 positive nodes with more than half patients (51.7%) having no further positive nodes in their final histopathology specimen. CONCLUSIONS: ANC should be a standard protocol in AUS positive patients as they invariably have high axillary disease burden while ANC can be omitted in case of select AUS negative and SLNB patients. However, further studies with more subjects may be require to substantiate the findings.


Subject(s)
Axilla/pathology , Breast Neoplasms, Male/pathology , Breast Neoplasms/pathology , Lymph Nodes/pathology , Axilla/diagnostic imaging , Biopsy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms, Male/diagnostic imaging , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Retrospective Studies , Sentinel Lymph Node Biopsy , Ultrasonography, Mammary
11.
Obes Surg ; 29(6): 1932-1936, 2019 06.
Article in English | MEDLINE | ID: mdl-30806915

ABSTRACT

BACKGROUND: British National guidelines (NICE) recommend bariatric surgery for patients with a body mass index (BMI) > 40 kg/m2, or BMI > 35 kg/m2 with any comorbidities of the metabolic syndrome. Intra-gastric balloons (IGB) can be used in super obese patients as a first step, before definitive surgery. AIMS: Quantify weight loss 6 months after IGB placement, measure progression to definitive surgery and identify complications. METHODS: Data collected retrospectively on 50 patients. Forty-six proposed for definitive bariatric surgery, four patients excluded. Analysis performed using SPSS v23.0. RESULTS: Median weight decreased from 165.5 to 155 kg (range 78 to 212, p < 0.01), BMI from 57.4 to 52.15 (range 32.9 to 70.5, p < 0.01), percentage excess weight loss (%EWL) was 12.9% (range - 3.3 to 64.66%, p < 0.01) and BMI reduction was 4.25 kg/m2 (range - 1.3 to 13.9, p < 0.01). Twenty-nine out of 46 patients (63%) progressed to definitive bariatric surgery. Ten out of 46 patients (21.7%) had complications requiring readmission. Seven of these patients required early balloon removal and six failed to progress to definitive surgery. Six patients had a second balloon placement, their actual weight loss was less successful, with some regaining weight. DISCUSSION: IGB is useful to aid weight loss prior to definitive bariatric surgery. Results from first balloon placement are encouraging and comparable with other studies "as reported by Genco et al. (Int J of Obes 30:129-133, 2006)." Readmission due to nausea, vomiting, dehydration and poor compliance may be associated with poor weight loss and failure to progress to definitive surgery. Second balloon placements were less successful. CONCLUSION: IGB as bridging therapy is a safe and useful adjunct. Sequential IGBs do not seem to provide additional benefit.


Subject(s)
Gastric Balloon , Obesity, Morbid/surgery , Weight Loss/physiology , Adult , Aged , Bariatric Surgery/statistics & numerical data , Body Mass Index , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
12.
J Clin Sleep Med ; 14(11): 1849-1857, 2018 11 15.
Article in English | MEDLINE | ID: mdl-30373688

ABSTRACT

STUDY OBJECTIVES: A single-item sleep quality scale (SQS) was developed as a simple and practical sleep quality assessment and psychometrically evaluated. METHODS: SQS measurement characteristics were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and morning questionnaire-insomnia (MQI) according to prespecified analysis plans in separate clinical studies of patients with insomnia and depression. Patients with insomnia (n = 70) received 4 weeks' usual care with an FDA-approved hypnotic agent; patients with depression (n = 651) received 8 weeks' active or experimental therapy. RESULTS: Concurrent criterion validity (correlation with measures of a similar construct) was demonstrated by strong (inverse) correlations between the SQS and MQI (week 1 Pearson correlation -.76) and PSQI (week 8 Goodman-Kruskal correlation -.92) sleep quality items in populations with insomnia and depression, respectively. In patients with depression, stronger correlations between the SQS and PSQI core sleep quality components versus other items supported convergent/divergent construct validity (similarity/dissimilarity to related/unrelated measures). Known-groups validity was evidenced by decreasing mean SQS scores across those who sleep normally, those borderline to having sleep problems, and those with problems sleeping. Test-retest reliability (intraclass correlation coefficient) was .62 during a 4-week period of sleep stability in patients with insomnia and .74 in stable patients with depression (1 week). Effect sizes (standardized response means) for change from baseline were 1.32 (week 1) and .67 (week 8) in populations with insomnia and depression, respectively. Mean SQS changes from baseline to week 8 convergently decreased across groups of patients with depression categorized by level of PSQI sleep quality improvement. CONCLUSIONS: The SQS possesses favorable measurement characteristics relative to lengthier or more frequently administered sleep questionnaires in patients with insomnia and depression. CLINICAL TRIAL REGISTRATION: Registry: ClincalTrials.gov, Title: Treatment of Patients With Major Depressive Disorder With MK0869, Identifier: NCT00034983, URL: https://clinicaltrials.gov/ct2/show/NCT00034983.


Subject(s)
Aprepitant/therapeutic use , Depressive Disorder, Major/diagnosis , Paroxetine/therapeutic use , Psychometrics/statistics & numerical data , Sleep Initiation and Maintenance Disorders/diagnosis , Surveys and Questionnaires , Adult , Aged , Comorbidity , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Hypnotics and Sedatives/therapeutic use , Male , Middle Aged , Reproducibility of Results , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/psychology
13.
J Immunol Methods ; 456: 61-66, 2018 05.
Article in English | MEDLINE | ID: mdl-29470976

ABSTRACT

Almost all immunological approaches [immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), Western blot], that are used to quantitate specific proteins have had to address high backgrounds due to non-specific reactivity. We report here for the first time a quantitative comparison of methods for reduction of the background of commercial biotinylated antibodies using the Python-based ELISA_QC program. This is demonstrated using a recombinant humanized anti-cocaine monoclonal antibody. Several approaches, such as adjustment of the incubation time and the concentration of blocking agent, as well as the dilution of secondary antibodies, have been explored to address this issue. In this report, systematic comparisons of two different methods, contrasted with other more traditional methods to address this problem are provided. Addition of heparin (HP) at 1 µg/ml to the wash buffer prior to addition of the secondary biotinylated antibody reduced the elevated background absorbance values (from a mean of 0.313 ±â€¯0.015 to 0.137 ±â€¯0.002). A novel immunodepletion (ID) method also reduced the background (from a mean of 0.331 ±â€¯0.010 to 0.146 ±â€¯0.013). Overall, the ID method generated more similar results at each concentration of the ELISA standard curve to that using the standard lot 1 than the HP method, as analyzed by the Python-based ELISA_QC program. We conclude that the ID method, while more laborious, provides the best solution to resolve the high background seen with specific lots of biotinylated secondary antibody.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Quality Control , Software , Antibodies, Monoclonal/analysis , Antibodies, Monoclonal/immunology , Cocaine/immunology , Heparin/chemistry , Heparin/immunology , Humans
14.
Biochem Biophys Res Commun ; 487(3): 690-694, 2017 06 03.
Article in English | MEDLINE | ID: mdl-28442345

ABSTRACT

We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [3H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy.


Subject(s)
Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Brain/immunology , Cocaine/chemistry , Cocaine/immunology , Tissue Banks , Antibodies, Monoclonal/genetics , Cloning, Molecular/methods , Drug Design , Metabolic Clearance Rate , Protein Binding , Protein Engineering/methods , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Tissue Distribution
15.
Sci Rep ; 7: 45257, 2017 03 28.
Article in English | MEDLINE | ID: mdl-28349934

ABSTRACT

Sporadic solar energetic particle (SEP) events affect the Earth's atmosphere and environment, in particular leading to depletion of the protective ozone layer in the Earth's atmosphere, and pose potential technological and even life hazards. The greatest SEP storm known for the last 11 millennia (the Holocene) occurred in 774-775 AD, serving as a likely worst-case scenario being 40-50 times stronger than any directly observed one. Here we present a systematic analysis of the impact such an extreme event can have on the Earth's atmosphere. Using state-of-the-art cosmic ray cascade and chemistry-climate models, we successfully reproduce the observed variability of cosmogenic isotope 10Be, around 775 AD, in four ice cores from Greenland and Antarctica, thereby validating the models in the assessment of this event. We add to prior conclusions that any nitrate deposition signal from SEP events remains too weak to be detected in ice cores by showing that, even for such an extreme solar storm and sub-annual data resolution, the nitrate deposition signal is indistinguishable from the seasonal cycle. We show that such a severe event is able to perturb the polar stratosphere for at least one year, leading to regional changes in the surface temperature during northern hemisphere winters.

16.
BMJ Case Rep ; 20172017 Jan 27.
Article in English | MEDLINE | ID: mdl-28130287

ABSTRACT

Post-traumatic abdominal aortic pseudoaneurysms remain a rare yet severe complication of aortic injuries and may present many years later. Clinical presentations vary, from the traditional aneurysmal symptoms of abdominal and/or back pain with or without a pulsatile mass, to a fatal rupture. We present the case of a man aged 42 years, with a history of blunt abdominal trauma 14 years ago, presenting with symptoms of non-specific lower abdominal pain and a recent history of straining due to constipation. Clinical examination revealed umbilical bruising, in keeping with Cullen's sign, and extensive postsacral bruising. This case highlights some of the atypical manifestations of aneurysmal rupture and the importance of early recognition and management.


Subject(s)
Abdominal Injuries/complications , Aneurysm, False/etiology , Aorta, Abdominal/diagnostic imaging , Aorta/injuries , Aortic Diseases/etiology , Aortic Rupture/etiology , Wounds, Nonpenetrating/complications , Adult , Aneurysm, False/diagnostic imaging , Aortic Diseases/diagnostic imaging , Aortic Rupture/diagnostic imaging , Humans , Male , Tomography, X-Ray Computed
18.
Sci Total Environ ; 563-564: 1016-29, 2016 Sep 01.
Article in English | MEDLINE | ID: mdl-27185349

ABSTRACT

The export of nitrogen (N), phosphorus (P), and suspended sediment (SS) is a long-standing management concern for the Chesapeake Bay watershed, USA. Here we present a comprehensive evaluation of nutrient and sediment loads over the last three decades at multiple locations in the Susquehanna River basin (SRB), Chesapeake's largest tributary watershed. Sediment and nutrient riverine loadings, including both dissolved and particulate fractions, have generally declined at all sites upstream of Conowingo Dam (non-tidal SRB outlet). Period-of-record declines in riverine yield are generally smaller than those in source input, suggesting the possibility of legacy contributions. Consistent with other watershed studies, these results reinforce the importance of considering lag time between the implementation of management actions and achievement of river quality improvement. Whereas flow-normalized loadings for particulate species have increased recently below Conowingo Reservoir, those for upstream sites have declined, thus substantiating conclusions from prior studies about decreased reservoir trapping efficiency. In regard to streamflow effects, statistically significant log-linear relationships between annual streamflow and annual constituent load suggest the dominance of hydrological control on the inter-annual variability of constituent export. Concentration-discharge relationships revealed general chemostasis and mobilization effects for dissolved and particulate species, respectively, both suggesting transport-limitation conditions. In addition to affecting annual export rates, streamflow has also modulated the relative importance of dissolved and particulate fractions, as reflected by its negative correlations with dissolved P/total P, dissolved N/total N, particulate P/SS, and total N/total P ratios. For land-use effects, period-of-record median annual yields of N, P, and SS all correlate positively with the area fraction of non-forested land but negatively with that of forested land under all hydrological conditions. Overall, this work has informed understanding with respect to four major factors affecting constituent export (i.e., source input, reservoir modulation, streamflow, and land use) and demonstrated the value of long-term river monitoring.


Subject(s)
Geologic Sediments/chemistry , Nitrogen/analysis , Phosphorus/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis , Environmental Monitoring , Hydrology , Maryland , Pennsylvania , Seasons
19.
Environ Sci Technol ; 50(4): 1877-86, 2016 Feb 16.
Article in English | MEDLINE | ID: mdl-26744776

ABSTRACT

Reduction of suspended sediment (SS), total phosphorus (TP), and total nitrogen is an important focus for Chesapeake Bay watershed management. The Susquehanna River, the bay's largest tributary, has drawn attention because SS loads from behind Conowingo Dam (near the river's mouth) have been rising dramatically. To better understand these changes, we evaluated histories of concentration and loading (1986-2013) using data from sites above and below Conowingo Reservoir. First, observed concentration-discharge relationships show that SS and TP concentrations at the reservoir inlet have declined under most discharges in recent decades, but without corresponding declines at the outlet, implying recently diminished reservoir trapping. Second, best estimates of mass balance suggest decreasing net deposition of SS and TP in recent decades over a wide range of discharges, with cumulative mass generally dominated by the 75∼99.5th percentile of daily Conowingo discharges. Finally, stationary models that better accommodate effects of riverflow variability also support the conclusion of diminished trapping of SS and TP under a range of discharges that includes those well below the literature-reported scour threshold. Overall, these findings suggest that decreased net deposition of SS and TP has occurred at subscour levels of discharge, which has significant implications for the Chesapeake Bay ecosystem.


Subject(s)
Bays/chemistry , Geologic Sediments/chemistry , Rivers/chemistry , Water Quality , Maryland , Nitrogen/analysis , Pennsylvania , Phosphorus/analysis
20.
Obes Surg ; 25(7): 1302-6, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25875353

ABSTRACT

BACKGROUND: Gastric band slippage is a significant challenge in gastric band surgery and can result in poor weight loss, pain and dysphagia, often requiring re-operation. The Royal Berkshire Hospital is one of 49 UK centres performing bariatric surgery. We audited our band slippage rates. METHODS: All patients undergoing gastric banding from February 2007 to December 2013 were included (follow-up until December 2014). Slip rate was calculated and compared to an audit standard (3.9 %). The impact of two interventions altering the method of band filling and post-operative dietary advice was studied. RESULTS: Initial slippage rates were high (17 %). Rates decreased following the interventions: 8.5 % by July 2012 (p = 0.05); 2.7 % by December 2014 (p = 0.2). CONCLUSIONS: Two simple, low-risk interventions have reduced complication rates in a high-risk population.


Subject(s)
Gastroplasty/adverse effects , Laparoscopy/adverse effects , Obesity, Morbid/surgery , Postoperative Complications/prevention & control , Adult , Female , Gastroplasty/methods , Humans , Laparoscopy/methods , Male , Middle Aged , Reoperation , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...